Epithelial-mesenchymal transition induced by bone morphogenetic protein 9 hinders cisplatin efficacy in ovarian cancer cells

Abstract

Bone morphogenetic protein 9 (BMP9) belongs to the transforming growth factor-β (TGF-β) superfamily, and has been reported to promote cancer cell proliferation and epithelial-mesenchymal transition (EMT). Cisplatin (DDP) is the first line treatment for ovarian cancer. However, initiation of EMT confers insensitivity to chemotherapy. The present study aimed to verify and examine the mechanisms underlying the effects of BMP9 on treatment with DDP for ovarian cancer. Prior to treatment with DDP, ovarian cancer cells were exposed to BMP9 for 3 days. Following this, cell viability, apoptosis rate and the extent of DNA damage were evaluated to compare the effects of DDP on BMP9-pretreated and non-pretreated ovarian cancer cells. In addition, EMT marker expression was evaluated by western blotting and immunofluorescence. The results demonstrated that BMP9 pretreatment inhibited the cytotoxicity of DDP on ovarian cancer cells. Additionally, BMP9-pretreated ovarian cancer cells had downregulated expression of the epithelial marker E-cadherin, which was accompanied by an upregulation of the mesenchymal markers N-cadherin, Snail, Slug, and Twist. Taken together, the findings of the present study indicated that BMP9 conferred resistance to DDP in ovarian cancer cells by inducing EMT. The present study provided valuable insight into the mechanisms of chemotherapy in ovarian cancer and highlighted the potential of BMP9 as a novel therapeutic target for improving cisplatin chemosen-sitivity.